If your symptoms are severe, call or go to the nearest emergency room. Taking it again could be fatal cause death. The use of drinks that contain alcohol can increase your risk of certain side effects from tramadol. These include slowed breathing, decreased heart rate, decreased blood pressure, or confusion.
You should not drink alcohol while taking tramadol. For people with seizures: If you have seizures or a history of seizures, tramadol can cause or worsen seizures. Talk with your doctor about whether tramadol is safe for you. For people with mental health problems: If you have thoughts about intentionally hurting yourself, or have hurt yourself, do not take tramadol. For people with addiction problems: If you have problems with addiction, such as addiction to alcohol or drugs, do not take tramadol.
Also avoid this drug if you have a history of addiction. For people with head injuries: Tramadol can increase the pressure inside your head. This can worsen your condition or make it harder for doctors to diagnose or find the cause of problems in your brain. For people with stomach problems: Tramadol can make certain stomach problems worse. It can also make it harder for doctors to diagnose or find the cause of problems. For people with breathing problems: Tramadol may slow your breathing and cause shallow breathing.
Shallow breathing means you take small, short breaths. If you already have a breathing problem, such as asthma, talk with your doctor about whether this drug is safe for you. For pregnant women: Tramadol is a category C pregnancy drug. That means two things:. This drug should only be used if the potential benefit justifies the potential risk to the fetus. Call your doctor right away if you become pregnant while taking this drug. For women who are breastfeeding: Tramadol may pass into breast milk and cause serious effects in a child who is breastfed.
These effects can include slowed breathing and death. Talk to your doctor if you breastfeed your child. For seniors: The kidneys or liver of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Seniors 65 years of age and older are at higher risk of side effects from the extended-release forms of this drug. Tramadol oral tablet is used for short-term or long-term treatment.
Your length of treatment depends on how severe your pain is. If you stop taking the drug suddenly, you may have symptoms of withdrawal, which can include:. For this drug to work well, a certain amount needs to be in your body at all times.
If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:. But if your symptoms are severe, call or go to the nearest emergency room right away. What to do if you miss a dose: Take your dose as soon as you remember. If you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects. A prescription for this medication is refillable.
Your doctor will write the number of refills authorized on your prescription. You or your pharmacy may have to contact your doctor for a new prescription if you need this medication refilled.
Your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include:. You may need to have blood tests during your treatment with tramadol. The cost of these tests will depend on your insurance coverage. Many insurance companies require a prior authorization for certain forms or brands of this drug.
Check your local drug store and clinics for take-back locations. You can also check the DEA web site for locations. Here is the link to the FDA safe disposal of medicines website: www. There is a problem with information submitted for this request. Sign up for free, and stay up-to-date on research advancements, health tips and current health topics, like COVID, plus expert advice on managing your health.
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This syndrome is often due to complex interactions between the consumed medications. Three key clinical features of this syndrome include:. Neuromuscular hyperactivity tremor, clonus, myoclonus, hyper-reflexia, stiffness, impaired coordination.
Autonomic hyperactivity profuse sweating, fever, tachycardia, tachypnea, chills, nausea, diarrhea, vomiting. Usually, SS happens after tramadol overdose or its concurrent use with other medications especially antidepressants; however, it may happen even after a single therapeutic dose of tramadol [ 5 , 98 , ]. Patients who consume mono amine oxidase MAO inhibitors are at the risk of development of SS [ 66 , ].
SS has been reported after concurrent use of tramadol with serotonin reuptake inhibitors SSRIs , venlafaxine, atypical antipsychotics, fluoxetine, sertraline, paroxetine, citalopram, fluvoxamine, moclobemide, clomipramine, mirtazapine, and tricyclic antidepressants [ 5 , 7 , 53 , 97 , ]. In patients who develop lethargy, hypotension, hypoxia, agitation, tachycardia, hypertension, confusion, hyperthermia, or hyper-reflexia, diagnosis of SS should be borne in mind [ 7 , , ].
Treatment is conservative and includes cessation of the culpable medication as well as administration of the antiserotonergics ciproheptadine, metisergide, propranolol, and chlorpromazine. Clinical manifestations recover within 24 hours except in those who have consumed medications with longer half-lives [ 5 , 53 , 97 ]. Pretreatment with chlordiazepoxide may prevent tramadol-induced SS [ 48 ].
Opioids metabolized by CYP including tramadol may induce many drug-drug interactions [ ]. In an Australian study, unwanted drug interactions were evaluated in patients who consumed antidepressants. As previously clarified, tramadol is similar to venlafaxine in structure and is believed to have antidepressant effects.
Venlafaxine can even cause false positive results for tramadol in urine tests [ 5 ]. Co-administration of tramadol and antidepressants especially TCAs, SSRIs, venlafaxine, bupropion, and phenothiazines should be performed cautiously because of the increased risk of seizure [ 6 , 25 , 72 ].
Concurrent administration of tramadol and NSAIDs can result in gastrointestinal hemorrhages due to severe platelet inhibition [ ]. Fatal toxicities have been reported after tramadol-TCA overdoses [ ].
It has been shown that tramadol-related mortality is more common after co-ingestion of benzodiazepines [ 8 , 26 ]. Tramadol can also interact with antitumor medications. For instance, tramadol decreases the efficacy of cisplatin by affecting gap junctions [ ]. In a case report, combination of paroxetine, dosulepin, and tramadol caused hallucination which improved after cessation of the medications [ ].
Fatalities have been reported after tramadol overdose or its co-ingestion with other medications. In most cases, death occurred after ingestion of high doses within 24 hours post-ingestion with really high blood levels [ 70 ]. Blood levels of tramadol have been between 0. The most common mechanisms of death after tramadol overdose are cardio-respiratory depression, resistant shock, asystole, and liver failure [ ]. Apnea may increase the risk of tramadol intoxication-related deaths [ 45 ].
Fatal toxicity of tramadol has been reported after co-administration of other medications including propranolol, trazodone, ethanol, and especially CNS depressants including benzodiazepines, barbiturates, and serotonergic drugs [ 88 ]. In fatal cases of tramadol, femoral blood samples are the best since they have the least redistribution changes after death [ ].
Tramadol may remain undetected in muscle samples after death due to its overdose [ ]. Mannocchi and assistants reported a case of death due to tramadol and propofol due to advanced severe dyspnea [ ]. A report showed nine deaths due to consumption of krypton a plant material containing ODT and mitragynine in whom the concentration of ODT was between 0.
Another study reported death due o tramadol because of respiratory depression accompanying GABA A and GABA B1 alpha1 over-expression in the ambiguus nucleus and medulla oblongata solitary. Table 3 [ ]. Accidental ingestion of tramadol is well tolerated by children [ 50 , 71 , ]. Side effects of tramadol seem to be more common but milder in children. Vomiting is especially common in them [ ]. Riedel and Stockhausen reported that tramadol could cross the blood brain barrier BBB in children and suppress the brain [ ].
Rectal administration of tramadol resulted in severe CNS depression in a 5-week-old infant which was explained to be due to the decreased kinetic elimination and increased permeability of the BBB [ 51 ]. Mazor et al. Short-term use of tramadol in lactating mother is not dangerous [ ] and the risk of neonatal dependency is low. Tramadol can cause SS without the effect of any other medication while in the adults the risk is increased if a SSRI is also taken [ 40 ].
In an 8-month-old infant with SS, the cause of hospital presentation was epistaxis. Sinus tachycardia, hyperthermia, hypertension, agitation, drowsiness, and hyper-reflexia of the lower extremities occurred within the first 24 hours after ingestion of mg of tramadol. Neurologic and cardiovascular effects recovered in two days. The infant was discharged after five days in good condition [ ].
Treatment should focus on conservative approaches including maintenance of airway, breathing, and circulation, oxygen therapy, fluid resuscitation, and diazepam administration to control agitation and seizure [ 6 , 14 , 36 ].
Patients should be monitored for increased CPK and possible acute renal failure that may happen within the next two days [ 6 , 14 ]. Hemodialysis should be considered in cases with acute renal failure and severe creatinine increase [ 14 ]. They may need intubation and ICU admission. Gastrointestinal decontamination should be performed in the patients who have referred within the first two hours post-ingestion and have no contraindications [ 8 , 49 , 50 ].
In severe toxicities due to ingestion of large amounts of sustained-release drug, multiple dose activated charcoal should be considered if no contraindication exists [ 6 , ]. In cases with resistant shock or asystole, extracorporeal methods may be needed [ 6 , 35 ]. Treatment of liver failure is conservative, as well, and urgent liver transplantation is not feasible in many cases [ 18 ].
In severe cases who have not even seized, experimental therapy with diazepam can be performed which can be of help in mild undiagnosed SS [ 6 , 44 ]. Treatment of SS in also conservative and includes withdrawal of the culpable drug and external cooling.
In a clinical study on patients, naloxone administration could induce seizure in tramadol-intoxicated patients [ 75 ]. Therefore, naloxone should not routinely be administered to treat decreased level of consciousness in tramadol toxicity unless respiratory depression has developed [ 21 , 45 ]. Seizures due to tramadol do not respond to naloxone but improve with administration of benzodiazepines. Naloxone can be considered for treatment of post-seizure complaints [ ].
Shadnia et al suggested that because of the low risk of multiple seizures in tramadol toxicity, anticonvulsant treatment should not be routinely given even in those with initial seizures [ 52 ]. Stoops et al evaluated naltrexone and showed that it could reverse the opioid-induced effects such as miosis; but, increased the serotonergic and adrenergic effects such as mydriasis [ 56 ]. Intravenous lipid emulsion ILE can reduce mortality due to acute toxicity of tramadol in rabbits, but increasing the ILE dose may cause reverse effects.
In a study on 30 rabbis, ILE reduced tramadol-induced tachycardia when administered within 30 minutes of poisoning and showed positive effects on normalizing mean arterial pressure and diastolic blood pressure but it did not have major effect on systolic blood pressure.
Intralipid also prevented tramadol-related seizures in low doses and reduced the frequency of increased CPK with higher doses [ ]. Although tramadol has less side effects, addicting capacity, and respiratory depression power in comparison with other opioids, many cases of dependency, abuse, intentional overdose, or poisoning have been reported following its use [ 20 , 27 , 48 , 56 , 70 , , , ].
Tramadol withdrawal lasts longer compared with other opioids [ ]. Where ultrarapid metabolizers are high in number, people are expected to have a higher risk of dependency to tramadol [ ]. Tramadol is as potent as heroin to cause euphoria [ 2 , 55 , ]. Withdrawal occurs after rapid abrupt discontinuation of tramadol with clinical manifestations including abdominal cramps, anxiety, skeletal pain, depression, diarrhea, goose flesh, insomnia, lacrimation, nausea, restlessness, rhinorrhea, and sweating.
The manifestations may sometimes be atypical and include hallucination, paranoia, panic attack, confusion, and atypical sensational experiences such as paresthesia, itching, tingling, delusion, depersonalization, derealization, and tinnitus [ 22 , 55 ].
Tramadol dependency happens faster in those who abuse it with other analgesics or ethanol [ 55 ]. Clinical therapeutic doses of tramadol may affect psychomotor and physiologic capacities of the patients who recreationally abuse it [ ].
Tramadol abuse in pregnancy may cause preterm labor and withdrawal manifestations in the newborn baby depending on the age of pregnancy, time elapsed since the beginning of tramadol use, dose of tramadol, CYP D2 polymorphism, development of the liver conjugation, and renal function of both mother and baby.
Attempts have been performed to treat this syndrome in neonates using clonidine alone or in combination with the thin opioid tinctures, chloral hydrate, benzodiazepines, and methadone [ 55 ]. In a study on patients with chronic non-cancer pain, it was shown that the frequency of abuse and dependency on tramadol and NSAIDs were the same and significantly less than hydrocodone [ ].
It is less dangerous to the organs in comparison with selective and nonselective NSAIDs and very powerful in the treatment of chronic pains [ ]. Tramadol can also be used in moderate to severe toothaches alone or in combination with acetaminophen or codeine [ , ]. In opioid-addicted patients, tramadol can be used for the treatment of withdrawal pain [ 68 ].
Tramadol in combination with paracetamol has a fair efficacy, immunity, and acceptance rate by the patients without development of dependency syndrome [ , , ]. Complications can be decreased by adding tramadol to the controlled medications [ ]. Monitoring of the liver function especially when the maximum daily doses are given is mandatory. Also, because of drug-drug interactions and differences in the individual metabolism and the chance of dependency, tramadol administration should be controlled by the treating physician.
If the patient is an opioid-addict, tramadol should not be administered unless absolutely indicated [ , ]. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers.
Login to your personal dashboard for more detailed statistics on your publications. Edited by Ana Cristina Andreazza. Edited by Theophile Theophanides. We are IntechOpen, the world's leading publisher of Open Access books.
Built by scientists, for scientists. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Introduction Poisoning is one of the leading causes of mortality and morbidity in many countries. Table 1. Studies on tramadol-induced seizures. Carcinogenic effects In long-term studies on rats and mice, no tramadol-attributed carcinogenic changes were detected.
Biochemical findings of tramadol Bleeding time BT , clotting time CT , prothrombin time, partial thromboplastin time, and body temperature were not affected by tramadol [ 17 ].
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